Circulatory endostatin level and risk of cardiovascular events in patients with end-stage renal disease on hemodialysis.

BACKGROUND: Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear. METHODS: A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events. RESULTS: Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables. CONCLUSION: Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.

Clinical significance of urinary inflammatory biomarkers in patients with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, although the definitive markers are unknown. We aimed to investigate the clinical significance of urinary cytokines in patients with IgAN. METHODS: From 2009 to 2018, the patients were divided into three groups: IgAN (n = 191), disease control (n = 53), and normal control (n = 76). We used a multiplex enzyme-linked immunosorbent assay to measure 16 selected urinary inflammatory cytokines, evaluated the correlation between clinical and pathological features following regression analysis on progression. RESULTS: The IgAN group exhibited significantly different levels of urinary cytokines compared to the normal control and disease control groups. Urinary levels of B-cell-activating factor, vascular endothelial growth factor receptor-2, monocyte chemoattractant protein-1, C-X-C motif chemokine 10, C-X-C motif ligand 16, epidermal growth factor (EGF), endocan, endostatin, growth/differentiation factor-15 (GDF-15), interleukin-6 (IL-6), mannose-binding lectin, transferrin receptor, and kidney injury molecule-1 were significantly correlated with both the estimated glomerular filtration rate and urine protein-creatinine ratio. In a multivariate Cox regression analysis, urinary EGF (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.17-0.95, P = 0.04), GDF-15 (HR 2.45, 95% CI 1.01-5.94, P = 0.048), and IL-6 (HR 3.02, 95% CI 1.05-8.64, P = 0.04) were associated with progression in IgAN. CONCLUSIONS: Urinary inflammatory biomarkers may serve as alternative predictive biomarkers in patients with IgAN. Further studies are needed to elucidate the physiological mechanisms and confirm the results.

Understanding the Korean dialysis cohort for mineral, vascular calcification, and fracture (ORCHESTRA) Study: Design, method, and baseline characteristics.

INTRODUCTION: End-stage renal disease (ESRD) is a growing disease in Korea and worldwide and is an important condition that affects patient outcomes. In order to provide optimal management for mineral disturbance, vascular calcification, and bone disease of ESRD patients, the ORCHESTRA study (Korean dialysis cohort for mineral, vascular calcification, and fracture) was conducted and enrolled Korean dialysis patients. METHODS: Sixteen university-affiliated hospitals and one Veterans Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive dialysis patients between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of patients were performed and their biospecimens were collected according to the study protocol. Primary outcomes were occurrence of major adverse cardiovascular events (MACE), invasive treatment for peripheral artery disease (PAD), and osteoporotic fractures. Secondary outcomes were hospitalization for cerebro-cardiovascular disease or progression of abdominal aortic calcification (AAC). Participants will be assessed for up to three years to determine whether primary or secondary outcomes occur. RESULTS: From May 2019 to January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of subjects was 60.4 ± 12.3 years. Males accounted for 57.7%. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group. CONCLUSION: This is a nationwide, multicenter, prospective cohort study that focuses on CKD-mineral and bone disorder (CKD-MBD) and aims to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients.

Neuronally differentiated macula densa cells regulate tissue remodeling and regeneration in the kidney.

Tissue regeneration is limited in several organs including the kidney, contributing to the high prevalence of kidney disease globally. However, evolutionary and physiological adaptive responses and the presence of renal progenitor cells suggest existing remodeling capacity. This study uncovered endogenous tissue remodeling mechanisms in the kidney that were activated by the loss of body fluid and salt and regulated by a unique niche of a minority renal cell type called the macula densa (MD). Here we identified neuronal differentiation features of MD cells that sense the local and systemic environment, secrete angiogenic, growth and extracellular matrix remodeling factors, cytokines and chemokines, and control resident progenitor cells. Serial intravital imaging, MD nerve growth factor receptor and Wnt mouse models and transcriptome analysis revealed cellular and molecular mechanisms of these MD functions. Human and therapeutic translation studies illustrated the clinical potential of MD factors including CCN1 as a urinary biomarker and therapeutic target in chronic kidney disease. The concept that a neuronally differentiated key sensory and regulatory cell type responding to organ-specific physiological inputs controls local progenitors to remodel or repair tissues may be applicable to other organs and diverse tissue regenerative therapeutic strategies.

Fasting blood glucose and the risk of all-cause mortality in patients with diabetes mellitus undergoing hemodialysis.

Background: Glycemic control is particularly important in hemodialysis (HD) patients with diabetes mellitus (DM). Although fasting blood glucose (FBG) level is an important indicator of glycemic control, a clear target for reducing mortality in HD patients with DM is lacking. Methods: A total of 26,162 maintenance HD patients with DM were recruited from the National Health Insurance Database of Korea between 2002 and 2018. We analyzed the association of FBG levels at the baseline health examination with the risk of all-cause and cause-specific mortality. Results: Patients with FBG 80100 mg/dL showed a higher survival rate compared with that of other FBG categories (p < 0.001). The risk of all-cause mortality increased with the increase in FBG levels, and adjusted hazard ratios (HRs) were 1.10 (95% confidence interval [CI], 1.04-1.17), 1.21 (95% CI, 1.13-1.29), 1.36 (95% CI, 1.26-1.46), and 1.61 (95% CI, 1.51-1.72) for patients with FBG 100-125, 125-150, 150-180, and ≥180 mg/dL, respectively. The HR for mortality was also significantly increased in patients with FBG < 80 mg/dL (adjusted HR, 1.14; 95% CI, 1.05-1.23). The analysis of cause-specific mortality also revealed a J-shaped curve between FBG levels and the risk of cardiovascular deaths. However, the risk of infection or malignancy-related deaths was not linearly increased as FBG levels increased. Conclusion: A J-shaped association was observed between FBG levels and the risk of all-cause mortality, with the lowest risk at FBG 80100 mg/dL in HD patients with DM.

Target blood pressure in Korean hemodialysis patients for optimal survival.

Background: Hypertension is a major cardiovascular risk factor in hemodialysis patients. This study identified the optimal blood pressure (BP) target for Korean hemodialysis patients using the Korean Renal Dialysis System (KORDS) dataset from the Korean Society of Nephrology and a pooled analysis for previous studies. Methods: Hemodialysis patients were classified according to their systolic (SBP) and diastolic BP (DBP) at intervals of 20 and 10 mmHg, respectively. As a primary and secondary outcome, all-cause mortality and cardiovascular mortality were evaluated. Subsequently, pooled analysis with previous literatures was performed. Results: Among 70,607 patients, 13,708 (19.4%) died in 2,426 days (interquartile range, 1,256-4,075 days). Mean SBP and DBP were 143.0 ± 19.6 and 78.5 ± 12.0 mmHg. In multivariable Cox regression, the patients with SBP of <120 and ≥180 mmHg showed 1.10- and 1.12-times increased risk of all-cause mortality compared to SBP of 120-140 mmHg. Meanwhile, DBP showed no significant association. In subgroup analysis, patients aged <70 years and without diabetes had a U-shaped SBP-mortality association. Cardiovascular mortality was increased in SBP of ≥160 mmHg compared to 120-140 mmHg, but it was not in <120 mmHg. Pooled analysis with previous studies mostly showed elevated risk in SBP of <120 mmHg, but the risks in 140-160 and 160-180 mmHg were not consistent. Conclusion: Extremely lowering BP (<120 mmHg) or uncontrolled hypertension (≥160 mmHg) should be avoided to optimize survival in Korean hemodialysis patients. Detailed analysis for patients with SBP of 120-160 mmHg should be studied further under uniform BP measurement, along with consideration of risk of intradialytic hypotension. Tailored recommendations regarding patient risk factors also should be considered.

Plant Extract-Derived Carbon Dots as Cosmetic Ingredients.

Plant extract-derived carbon dots (C-dots) have emerged as promising components for sustainability and natural inspiration to meet consumer demands. This review comprehensively explores the potential applications of C-dots derived from plant extracts in cosmetics. This paper discusses the synthesis methodologies for the generation of C-dots from plant precursors, including pyrolysis carbonization, chemical oxidation, hydrothermal, microwave-assisted, and ultrasonic methods. Plant extract-derived C-dots offer distinct advantages over conventional synthetic materials by taking advantage of the inherent properties of plants, such as antioxidant, anti-inflammatory, and UV protective properties. These outstanding properties are critical for novel cosmetic applications such as for controlling skin aging, the treatment of inflammatory skin conditions, and sunscreen. In conclusion, plant extract-derived C-dots combine cutting-edge nanotechnology and sustainable cosmetic innovation, presenting an opportunity to revolutionize the industry by offering enhanced properties while embracing eco-friendly practices.

Comparison of Humoral Response between Third and Fourth Doses of COVID-19 Vaccine in Hemodialysis Patients.

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection.

Clinical significance of urinary exosomal microRNAs in patients with IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. The clinical relevance of 11 urinary exosomal microRNAs (miRNAs) was evaluated in patients with IgAN. From January 2009 to November 2018, IgAN (n = 93), disease control (n = 11), and normal control (n = 19) groups were enrolled. We evaluated the expression levels of urinary exosomal miRNAs at the baseline and their relationship with clinical and pathologic features. This study aimed to discriminate statistically powerful urinary exosomal miRNAs for the prognosis of IgAN. Urinary miRNA levels of miR-16-5p, miR-29a-3p, miR-124-3p, miR-126-3p, miR-199a-3p, miR-199b-5p, and miR-335-3p showed significant correlation with both estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (uPCR). In univariate regression analysis, age, body mass index, hypertension, eGFR, uPCR, Oxford classification E, and three miRNAs (miR-16-5p, miR-199a-3p, and miR-335-3p) were associated with disease progression in patients with IgAN. The area under the curve (AUC) of miR-199a-3p was high enough (0.749) without any other clinical or pathologic factors, considering that the AUC of the International IgAN Risk Prediction Tool was 0.853. Urinary exosomal miRNAs may serve as alternative prognostic biomarkers of IgAN with further research.

A Bioactive Compound-Loaded Zinc-Aminoclay Encapsulated, Pickering Emulsion System for Treating Acne-Inducing Microbes.

Acne is a common skin condition caused by the growth of certain bacteria. Many plant extracts have been investigated for their potential to combat acne-inducing microbes, and one such plant extract is microwave-assisted Opuntia humifusa extract (MA-OHE). The MA-OHE was loaded onto zinc-aminoclay (ZnAC) and encapsulated in a Pickering emulsion system (MA-OHE/ZnAC PE) to evaluate its therapeutic potential against acne-inducing microbes. Dynamic light scattering and scanning electron microscopy were used to characterize MA-OHE/ZnAC PE with a mean particle diameter of 353.97 nm and a PDI of 0.629. The antimicrobial effect of MA-OHE/ZnAC was evaluated against Staphylococcus aureus (S. aureus) and Cutibacterium acnes (C. acnes), which contribute to acne inflammation. The antibacterial activity of MA-OHE/ZnAC was 0.1 and 0.025 mg/mL to S. aureus and C. acnes, respectively, which were close to naturally derived antibiotics. Additionally, the cytotoxicity of MA-OHE, ZnAC, and MA-OHE/ZnAC was tested, and the results showed that they had no cytotoxic effects on cultured human keratinocytes in a range of 10-100 µg/mL. Thus, MA-OHE/ZnAC is suggested to be a promising antimicrobial agent for treating acne-inducing microbes, while MA-OHE/ZnAC PE is a potentially advantageous dermal delivery system.

Corrigendum: Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients.

[This corrects the article DOI: 10.3389/fimmu.2023.1190576.].

Discordant renal progression of Fabry disease in male monozygotic twins: a case report.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A (α-GAL). Clinical phenotypes tend to vary in monozygotic female twins because mutations are located on the X-chromosome, whereas similar phenotypes are found in male monozygotic twins. Here we report the case of male monozygotic twins with FD presenting with distinguishable renal phenotypes. Case: A 49-year-old male patient who visited the hospital with proteinuria 14 years prior was readmitted for the same issue. His monozygotic twin brother had started hemodialysis 6 months prior due to renal failure of unknown origin. The patient's renal function was within the normal range, while his spot urine protein-to-creatinine ratio was 557 mg/g. Echocardiography revealed left ventricular hypertrophy (LVH). The findings of a renal biopsy were consistent with FD. Genetic testing identified a c.656T>C mutation in the GLA gene, and α-GAL activity was significantly decreased. Genetic screening of his family clarified that his mother, older sister, twin brother, and his daughter had the same genetic mutations. The patient received enzyme replacement therapy 34 times. Subsequently, migalastat was initiated that continues today. Renal function and proteinuria remain stable, and the LVH has mildly improved. Conclusion: This is the first case of male monozygotic twins expressing different progressions of FD. Our findings demonstrate the possibility that environmental or epigenetic factors may critically influence genotype-phenotype discordance.

Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients.

Introduction: Acute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR. Materials and methods: Candidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort. Results: We identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77). Conclusion: We have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients.

Clinical implications of circulating follistatin-like protein-1 in hemodialysis patients.

Follistatin-like protein-1 (FSTL-1) is secreted glycoprotein, which regulates cardiovascular, immune and skeletal system. However, the clinical significance of circulating FSTL-1 levels remains unclear in hemodialysis patients. A total 376 hemodialysis patients were enrolled from June 2016 to March 2020. Plasma FSTL-1 level, inflammatory biomarkers, physical performance, and echocardiographic findings at baseline were examined. Plasma FSTL-1 levels were positively correlated with TNF-α and MCP-1. Handgrip strength showed weak positive correlation in male patients only, and gait speed showed no correlation with FSTL-1 levels. In multivariate linear regression analysis, FSTL-1 level was negatively associated with left ventricular ejection fraction (ß = - 0.36; p = 0.011). The cumulative event rate of the composite of CV event and death, and cumulative event rate of CV events was significantly greater in FSTL-1 tertile 3. In multivariate Cox-regression analysis, FSTL-1 tertile 3 was associated with a 1.80-fold risk for the composite of CV events and death(95% confidence interval (CI) 1.06-3.08), and a 2.28-fold risk for CV events (95% CI 1.15-4.51) after adjustment for multiple variables. In conclusion, high circulating FSTL-1 levels independently predict the composite of CV events and death, and FSTL-1 level was independently associated with left ventricular systolic dysfunction.

Antioxidants for improved skin appearance: Intracellular mechanism, challenges and future strategies.

Recent advances in molecular and biochemical processes relevant to the skincare field have led to the development of novel ingredients based on antioxidants that can improve skin health and youthfulness. Considering the plethora of such antioxidants and the many implications for the skin's appearance, this review focuses on describing the critical aspects of antioxidants, including cosmetic functions, intracellular mechanisms and challenges. In particular, specialized substances are suggested for the treatment of each skin condition, such as skin ageing, skin dehydration and skin hyperpigmentation, which treatments can maximize effectiveness and avoid side effects during skin care processes. In addition, this review proposes advanced strategies that either already exists in the cosmetic market or should be developed to improve and optimize cosmetic' beneficial effects.

Les progrès récents des processus moléculaires et biochimiques pertinents pour le domaine des soins de la peau ont conduit au développement de nouveaux ingrédients à base d'antioxydants qui peuvent améliorer la santé et la jeunesse de la peau. Compte tenu de la pléthore de ces antioxydants et des nombreuses implications pour l'apparence de la peau, cette revue se concentre sur la description des aspects critiques des antioxydants, pour le domaine de la cosmétique, pour les mécanismes intracellulaires et les défis à surmonter. En particulier, des substances spécialisées sont suggérées pour le traitement de chaque affection cutanée, comme le vieillissement cutané, la déshydratation cutanée et l'hyperpigmentation cutanée, lesquels traitements peuvent maximiser l'efficacité et éviter les effets secondaires pendant les processus de soins de la peau. De plus, cette revue propose des stratégies avancées qui existent déjà sur le marché des cosmétiques ou qui devraient être développées pour améliorer et optimiser les effets bénéfiques des cosmétiques.

Beneficial Effects of Opuntia humifusa (Korean Cheonnyuncho) on Human Health Based on Antioxidant Properties: Systematic Review and Meta-Analysis.

In this study, a systematic review and meta-analysis are conducted to evaluate the medical applications of Opuntia humifusa (OH). A total of 171 articles are peer-reviewed; however, only 15 individual studies were included after the manual screening to eliminate unnecessary studies. A comparative standardized means difference (SMD) between the OH and control groups is used as a parameter to demonstrate the beneficial effects of OH for skin aging, cancer, and diabetes treatments based on its antioxidant activities. The OH treatment exhibits positive results in improving collagen synthesis and demonstrates that it is nontoxic to normal human cells without analytical heterogeneity (SMD = 1.18 [0.11, 2.26] and I2 = 0%). Moreover, the results confirm the effectiveness of OH treatment on downregulatory cancers in terms of decreased cancer cell proliferation and tumor weight and increased numbers of cancer cells in the apoptosis phase (pooled SMD = -1.17 [-1.72, -0.62]). However, this comparison does not yield a statistically significant result (I2 = 69%). Additionally, the OH treatment is found to reduce the symptoms of diabetes in diabetic rats, particularly by lowering glucose and triglyceride levels and increasing high-density lipoprotein cholesterol levels. This study suggests that OH extracts are helpful for the prevention of human diseases and might be potential candidates for future medicines.

Correction: Kim et al. The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins. Toxins 2022, 14, 779.

In the original publication [...].

High physical activity alleviates the adverse effect of higher sedentary time on the incidence of chronic kidney disease.

BACKGROUND: Low physical activity (PA) increases the prevalence of chronic kidney disease (CKD). This study aimed to investigate the effects of PA and sedentary time (ST) on the changes in renal function and the development of CKD in the middle-aged Korean population. METHODS: From the Korean Genome and Epidemiology Study Database, 7988 participants in their 40s and 60s were identified and stratified by (1) PA: high-PA (>24 MET-h/day), moderate-PA (9-24 MET-h/day) and low-PA (<9 MET-h/day); and (2) ST: high-ST (>6 h/day), moderate-ST (3-6 h/day) and low-ST (<3 h/day). Incident CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 following the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: The mean age of the participants was 52.0 years. The overall incidence of CKD was 16.8 per 1000 person-years over a median of 12 years. The lower the PA and the higher the ST, the lower the baseline eGFR. Relative to the high-PA, the coefficients of the annual eGFR decline were -0.12 (95% confidence interval [CI]: -0.26 to 0.001, P = 0.081) and -0.13 (95% CI: -0.27 to 0.01, P = 0.078) in the moderate- and low-PA groups, respectively. Similarly, relative to the low-ST, the coefficients of annual eGFR decline were -0.07 (59% CI: -0.19 to 0.05, P = 0.236) and -0.14 (95% CI: -0.28 to -0.01, P = 0.039) in the moderate- and high-ST groups, respectively. Incident CKD was higher with lower PA (hazard ratio: high-PA 1.00, moderate-PA 1.13 [1.00, 1.28, P = 0.056] and low-PA 1.25 [1.11, 1.24, P < 0.001]) and higher ST (hazard ratio: low-ST 1.00, moderate-ST 1.04 [0.94, 1.16, P = 0.440] and high-ST 1.19 [1.05, 1.34, P = 0.007]). The high-PA reduced the risk for the CKD development irrespective of the amount of ST. CONCLUSIONS: Low-PA and high-ST are risk factors for the development of CKD in the middle-aged Korean population. High-PA recovers high-ST, inducing a harmful effect on the occurrence of CKD.

Utilization of light-emitting diodes for skin therapy: Systematic review and meta-analysis.

This study investigates the dermatological as well as the esthetic potential of light-emitting diodes (LEDs) by performing a systematic review and meta-analysis. From the electronic databases, 554 articles were assessed; however, only 31 studies were selected after manually screening and eliminating unnecessary studies. The potential effectiveness of LEDs for skin therapies was assessed by evaluating the standardized mean differences (SMDs) and funnel plots of this meta-analysis. It was discovered that both red and blue LED lights play an important role in the treatment of acne vulgaris with an overall statistically significant SMD of -2.42 [-2.64, -2.15] and I2  = 17% < 50%. Additionally, other LEDs (e.g., yellow LEDs and near-infrared devices) showed outstanding levels of effectiveness, not only in reducing the lesions of herpes simplex and psoriasis but also in improved skin rejuvenation with highly consistent analytical results (I2  = 0% and 33%, respectively). However, the analysis of LED-based skin wound healing and atopic dermatitis treatments exhibited heterogeneity (I2  = 85% and 90%) due to the lack of unpublished articles. In conclusion, it is suggested that LEDs are useful for dermatology and could be potential candidates for future cosmetic applications.

Urine Exosomal bkv-miR-B1-5p and BK Virus Nephropathy in Kidney Transplant Recipients.

BACKGROUND: Urine exosomal bkv-miR-B1-5p is associated with BK virus (BKV) nephropathy (BKVN); however, its posttransplantation changes and predictability for BKVN have not been determined in kidney transplant recipients (KTRs). METHODS: Urine exosomal bkv-miR-B1-5p and urine and plasma BKV DNA were measured at 2 weeks and 3, 6, and 12 months posttransplant in 83 KTRs stratified into biopsy-proven or presumptive BKVN, BKV viruria, and no evidence of BKV reactivation. Joint model, multivariable Cox model and receiver operating characteristic curve (ROC) were used to investigate the association of each assay with the following events: a composite of biopsy-proven or presumptive BKVN, and biopsy-proven BKVN. RESULTS: Urine exosomal bkv-miR-B1-5p and urine and plasma BKV DNA showed similar posttransplant time-course changes. Joint models incorporating serial values demonstrated significant associations of all assays with the events, and Cox analyses using single time point values at 2 weeks posttransplant showed that only urine exosomal bkv-miR-B1-5p was significantly associated with the events, although it did not outperform urine BKV DNA in ROC analyses. CONCLUSIONS: Urine exosomal bkv-miR-B1-5p was associated with BKVN as were urine and plasma BKV DNA loads on serial follow-up, and might have potential as a predictive marker for BKVN during the early posttransplant period. CLINICAL TRIALS REGISTRATION: Clinical Research Information Service (https://cris.nih.go.kr/cris/), KCT0001010.